9jao

Structural highlights

Disease

SMRCD_HUMAN Huriez syndrome;Isolated congenital adermatoglyphia;Absence of fingerprints-congenital milia syndrome. The disease is caused by mutations affecting the gene represented in this entry. Splice site mutations causing aberrant splicing of skin-specific isoform 3 are likely to exert a loss-of-function effect and are involved in ADERM.^{[1] [2]} The disease is caused by mutations affecting the gene represented in this entry. Splice site mutations causing aberrant splicing of skin-specific isoform 3 are likely to exert a loss-of-function effect and are involved in BSNS.^{[3] [4]}

Function

SMRCD_HUMAN DNA helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization. Promotes DNA end resection of double-strand breaks (DSBs) following DNA damage: probably acts by weakening histone DNA interactions in nucleosomes flanking DSBs. Required for the restoration of heterochromatin organization after replication. Acts at replication sites to facilitate the maintenance of heterochromatin by directing H3 and H4 histones deacetylation, H3 'Lys-9' trimethylation (H3K9me3) and restoration of silencing.^{[5] [6]}

References

1. ↑ Nousbeck J, Burger B, Fuchs-Telem D, Pavlovsky M, Fenig S, Sarig O, Itin P, Sprecher E. A mutation in a skin-specific isoform of SMARCAD1 causes autosomal-dominant adermatoglyphia. Am J Hum Genet. 2011 Aug 12;89(2):302-7. doi: 10.1016/j.ajhg.2011.07.004. Epub, 2011 Aug 4. PMID:21820097 doi:http://dx.doi.org/10.1016/j.ajhg.2011.07.004
2. ↑ Nousbeck J, Sarig O, Magal L, Warshauer E, Burger B, Itin P, Sprecher E. Mutations in SMARCAD1 cause autosomal dominant adermatoglyphia and perturb the expression of epidermal differentiation-associated genes. Br J Dermatol. 2014 Dec;171(6):1521-4. doi: 10.1111/bjd.13176. Epub 2014 Oct 26. PMID:24909267 doi:http://dx.doi.org/10.1111/bjd.13176
3. ↑ Marks KC, Banks WR 3rd, Cunningham D, Witman PM, Herman GE. Analysis of two candidate genes for Basan syndrome. Am J Med Genet A. 2014 May;164A(5):1188-91. doi: 10.1002/ajmg.a.36438. Epub 2014 , Mar 24. PMID:24664640 doi:http://dx.doi.org/10.1002/ajmg.a.36438
4. ↑ Li M, Wang J, Li Z, Zhang J, Ni C, Cheng R, Yao Z. Genome-wide linkage analysis and whole-genome sequencing identify a recurrent SMARCAD1 variant in a unique Chinese family with Basan syndrome. Eur J Hum Genet. 2016 Aug;24(9):1367-70. doi: 10.1038/ejhg.2016.15. Epub 2016 Mar, 2. PMID:26932190 doi:http://dx.doi.org/10.1038/ejhg.2016.15
5. ↑ Rowbotham SP, Barki L, Neves-Costa A, Santos F, Dean W, Hawkes N, Choudhary P, Will WR, Webster J, Oxley D, Green CM, Varga-Weisz P, Mermoud JE. Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1. Mol Cell. 2011 May 6;42(3):285-96. doi: 10.1016/j.molcel.2011.02.036. PMID:21549307 doi:http://dx.doi.org/10.1016/j.molcel.2011.02.036
6. ↑ Costelloe T, Louge R, Tomimatsu N, Mukherjee B, Martini E, Khadaroo B, Dubois K, Wiegant WW, Thierry A, Burma S, van Attikum H, Llorente B. The yeast Fun30 and human SMARCAD1 chromatin remodellers promote DNA end resection. Nature. 2012 Sep 27;489(7417):581-4. doi: 10.1038/nature11353. Epub 2012 Sep 9. PMID:22960744 doi:http://dx.doi.org/10.1038/nature11353